Table 2.
Impact of Viscosity Modifying Agents on pH, Osmolality, Viscosity, Injection Forces and Accelerated (25 °C/60% RH) Stability of IgG1 DS Formulation at ~200 mg/mL Concentration up to 6 Months.
| Excipients Used as Viscosity Modifiers (and their Concentration in mg/mL) | pH | Osmolality (mOsmols/kg) | Viscosity in cps at 25 °C | Injection Forces (N) |
% High Molecular Weight Impurities |
% Monomer |
% Low Molecular Weight Impurities |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Glide Force | Break-Loose Force | Day 0 | 3 Month | 6 Month | Day 0 | 3 Month | 6 Month | Day 0 | 3 Month | 6 Month | ||||
| IgG1 Drug Substance at ~200 mg/mL (NIL) | 6.07 | 70 | 21.9 | 9.5 | 5.5 | 0.4 | 1.9 | 2.0 | 99.4 | 96.4 | 93.8 | 0.2 | 1.7 | 4.2 |
| Arginine HCl (54.7 mg/mL) | 6.03 | 285 | 16.7 | 3.8 | 3.0 | 0.6 | 1.0 | 1.3 | 99.4 | 93.3 | 90.0 | 0.0 | 5.7 | 8.7 |
| Ammonium chloride (13.9 mg/mL) | 6.06 | 300 | 13.4 | 4.5 | 2.3 | 0.7 | 1.4 | 1.4 | 99.4 | 92.8 | 84.8 | 0.0 | 5.8 | 13.7 |
| Sodium chloride (15.2 mg/mL) | 6.07 | 303 | 15.0 | 5.4 | 2.7 | 0.7 | 1.1 | 1.4 | 99.2 | 93.5 | 87.7 | 0.1 | 5.4 | 11.0 |
| Magnesium chloride (25 mg/mL) | 6.07 | 285 | 19.9 | 5.3 | 2.5 | 1.3 | 1.1 | 1.2 | 98.7 | 93.7 | 88.0 | 0.0 | 3.9 | 10.7 |
| Calcium chloride (14.4 mg/mL) | 6.14 | 380 | 11.1 | 4.8 | 2.6 | 1.7 | 2.0 | 2.1 | 98.2 | 96.5 | 94.0 | 0.1 | 1.6 | 3.9 |
| Glycine (9.8 mg/mL) | 6.27 | 291 | 13.6 | 4.2 | 5.0 | 0.7 | 1.7 | 1.4 | 99.3 | 96.3 | 95.1 | 0.1 | 2.0 | 3.5 |
| Proline (15 mg/mL) | 6.20 | 320 | 11.3 | 5.7 | 5.1 | 0.6 | 1.3 | 1.4 | 99.3 | 97.0 | 94.7 | 0.1 | 1.8 | 3.9 |